E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Immunofediciency (PID) syndromes |
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E.1.1.1 | Medical condition in easily understood language |
Primary immune deficiency (PID) diseases are a group of potentially serious disorders in which inherited defects in the immune system lead to increased infections. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10036700 |
E.1.2 | Term | Primary immunodeficiency syndromes |
E.1.2 | System Organ Class | 100000004870 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to assess the efficacy of LFB-IgSC. |
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E.2.2 | Secondary objectives of the trial |
There are two secondary objectives:
- To assess the safety of LFB-IgSC,
- To assess the pharmacokinetic profile of LFB-IgSC over a one-week injection interval.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female aged from 2 to 70 years old
- Primary immunodeficiency syndrome with predominant antibody deficiency as: X-linked agammaglobulinaemia (XLA), Common variable immunodeficiency (CVID), Other PID syndrome in which the main immunological defect is deficiency in IgG production.
- Stable IgG therapy for at least 5 months before the study, with a constant dose ranging from 0.2 to 0.8 g/kg per month and with regular intervals of 3 to 4 weeks for IVIg and one week for SCIg.
- At least 2 documented serum IgG trough levels ≥ 5 g/l with the previous IgG dosage regimen.
- For women of childbearing potential, negative blood pregnancy test at enrolment and agreement to use a medically-acceptable method of contraception throughout the study.
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E.4 | Principal exclusion criteria |
- History of severe allergy or serious adverse reaction to any IVIg, SCIg or an excipient of LFB-IgSC.
- Patient with known antibodies to IgA.
- Glomerular filtration rate < 80 ml/min/1.73m2 measured according to the Modified Diet in Renal Disease (MDRD) calculation.
- Progressive hepatic disease that could worsen during the study.
- Refusal of PK study (for adults only).
- History of cardiac ischemia, cardiac insufficiency, cerebral ischemia, stroke, thrombotic events or pulmonary embolism.
- Any additional cause of immunodeficiency, other than a primary immunodeficiency, (such as acquired immunodeficiency or malignancy of lymphoid cells).
- Allogenic haematopoietic stem cell transplantation.
- Need for routine premedication before SCIg infusions (excluding dermal anaesthetics).
- Need for long-term therapy with corticosteroids or prophylactic antibiotics during the study.
- Immunosuppressive agents, including anti-CD20 antibodies, during the last 6 months. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the number of serious bacterial infections (SBI) per patient and per year (annualized rate) as defined:
- Bacteraemia or sepsis
- Bacterial meningitis
- Osteomyelitis / septic arthritis
- Bacterial pneumonia
- Visceral abscess
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout the course of the study |
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E.5.2 | Secondary end point(s) |
Secondary efficacy endpoints
- Rate of infections (serious or non-serious) per patient and per year
- Number of days missed from work or school due to infections,
- Number of days of hospitalization related to infection,
- Number of days with use of antibiotics,
- Number of fever episodes (>38°C) related to infections,
- Total IgG trough levels will be assessed every month over a period of 6 months starting at week 21. These IgG trough levels will be compared to trough levels obtained with the previous immunoglobulin (IVIg or SCIg). In addition, distribution of IgG sub-classes will be described.
Safety endpoints
- Number of patients who have presented an AE and number of AEs:
For all AEs reported during the study
For IMP related AEs
For infusional AEs i.e., AEs that begin during or within 72 hours after an infusion
For local reactions to IMP
For serious AEs
- Percentage of site-infusions with site reaction
- Changes in vital signs from before infusions to after infusions.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Total IgG trough levels: every month over a period of 6 months starting at W21.
- All other secondary endpoints: throughout the course of the study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase III with first administration to humans |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Germany |
Hungary |
Italy |
Poland |
Ukraine |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |